Astrocyte and glutamate involvement in the pathogenesis of epilepsy in Alzheimer's disease

Abstract

Alzheimer's disease (AD) can increase the risk of epilepsy by up to 10-fold compared to healthy age-matched controls. However, the pathological mechanisms that underlie this increased risk are poorly understood. Because disruption in brain glutamate homeostasis has been implicated in both AD and epilepsy, this might play a mechanistic role in the pathogenesis of epilepsy in AD. Prior to the formation of amyloid beta (Aβ) plaques, the brain can undergo pathological changes as a result of increased production of amyloid precursor protein (APP) and Aβ oligomers. Impairments in the glutamate uptake ability of astrocytes due to astrogliosis are hypothesized to be an early event occurring before A..